Method and apparatus for treating dermal melasma

ABSTRACT

Exemplary methods and devices can be provided for improving the appearance of dermal melasma. This can be done, e.g., focusing electromagnetic radiation having a wavelength between about 600 nm and 850 nm into a region of the pigmented dermal tissue at a depth between about 150 and 400 microns, using a lens arrangement having a large numerical aperture between about 0.5 and 0.9. The exemplary local dwell time of the focused radiation can be less than a few milliseconds, and a local fluence provided in the focal region can be between about 50 and 500 J/cm2. The focal region can be scanned through the dermal tissue at speeds on the order of a few cm/s. Such parameters can provide sufficient energy absorption by pigmented cells in the dermis to disrupt them while avoiding damage to the overlying tissue and unpigmented dermal tissue.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application is a continuation of U.S. patent applicationSer. No. 14/911,169 filed Feb. 9, 2016, which issues as U.S. Pat. No.11,083,523 on Aug. 10, 2021, which is a U.S. National Phase of, andrelates to and claims priority from International Patent Application No.PCT/US2014/050518 filed on Aug. 11, 2014 and published as WO 2015/021462on Feb. 12, 2015, and claims priority from U.S. Provisional PatentApplication Ser. No. 61/864,238 filed Aug. 9, 2013, the entiredisclosures of which are incorporated herein by reference in theirentireties.

FIELD OF THE DISCLOSURE

Exemplary embodiments of the present disclosure relates to treatingpigmented tissue, and more particularly to methods and apparatus fortreating dermal melasma.

BACKGROUND INFORMATION

Melasma is a skin disorder of unknown etiology that causes a blotchyhyperpigmentation, often in the facial area. This condition is morecommon in women than in men. Although the specific cause(s) of melasmamay not be well-understood, the pigmented appearance of melasma can beaggravated by certain conditions such as pregnancy, sun exposure,certain medications, such as, e.g., oral contraceptives, hormonallevels, genetics, etc.

Exemplary symptoms of melasma include dark, irregularly-shaped patchesor macules, which are commonly found on the upper cheek, nose, upperlip, and forehead. These patches often develop gradually over time.Melasma does not appear to cause any other symptoms, nor have otherdetrimental effects, beyond the cosmetic discoloration.

Unlike many pigmented structures that are typically present in theepidermal region of skin (i.e., at or near the skin surface), dermal (ordeep) melasma is often characterized by widespread presence of melaninand melanophages (including, e.g., excessively-pigmented cells) inportions or regions of the underlying dermis. Accordingly, treatment ofdermal melasma (e.g., lightening of the appearance of darkened pigmentedregions) can be particularly challenging because of the presence of thegreater difficulty in accessing and affecting such pigmented cells andstructures located deeper within the skin. Accordingly, conventionalskin rejuvenation treatments such as facial peels (laser or chemical),dermabrasion, topical agents, and the like, which primarily affect theoverlying epidermis, may not be effective in treating dermal melasma.

It has been observed that application of light or optical energy ofcertain wavelengths can be strongly absorbed by pigmented cells, therebydamaging them. However, an effective treatment of dermal melasma usingoptical energy introduces several obstacles. For example, pigmentedcells in the dermis must be targeted with sufficient optical energy ofappropriate wavelength(s) to disrupt or damage them, which may releaseor destroy some of the pigmentation and reduce the pigmented appearance.However, such energy can be absorbed by pigment (e.g., chromophores) inthe overlying skin tissue, such as the epidermis and upper dermis. Thisnear-surface absorption can lead to excessive damage of the outerportion of the skin, and insufficient delivery of energy to the deeperdermis to affect the pigmented cells therein.

Fractional approaches have been developed that involve application ofoptical energy to small, discrete locations on the skin that areseparated by healthy tissue to facilitate healing. However, suchfractional approaches may “miss” many of the pigmented cells in thedermis, and effective targeting of such deeper cells may again result inexcessive damage to the nearby healthy tissue.

Therefore, it may be desirable to provide method and apparatus that caneffectively target pigmented cells in the dermis and reduce theappearance of melasma, without generating excessive damage to healthyskin tissue or producing other undesirable side effects.

SUMMARY OF EXEMPLARY EMBODIMENTS OF THE DISCLOSURE

Exemplary embodiments of methods and apparatus can be provided for atreatment of dermal melasma and other pigmented defects within thedermis, e.g., to lighten the dark pigmented appearance of dermalmelasma. The exemplary embodiments of the methods and apparatus canfacilitate selective energy absorption by, and thermal damage to,pigmented structures within the dermis by focusing highly-convergentelectromagnetic radiation (EMR), e.g., optical energy, havingappropriate wavelengths onto the pigmented regions within the dermis.This exemplary procedure can result in heating and/or thermal damage tothe pigmented regions, thereby disrupting the pigment and lightening theappearance of the skin, while avoiding unwanted thermal damage tosurrounding unpigmented tissue and the overlying tissue.

According to exemplary embodiments of the present disclosure, anapparatus can be provided that can include a radiation emitterarrangement configured to emit EMR, and an optical arrangementconfigured to direct the EMR onto the skin being treated and focus it toa focal region within the dermis. A plate that is substantiallyoptically transparent to the EMR can be provided on a portion of theapparatus that is configured to contact the surface of the skin beingtreated. Such plate can stabilize the pliable skin tissue and facilitatebetter control of the depth of the focal region below the skin surface.A lower surface of the plate can be substantially planar, or it mayoptionally be slightly convex or concave. The apparatus can furtherinclude a housing or handpiece that can contain these components andfacilitate manipulation of the apparatus during its use.

The EMR emitter can include, e.g., a waveguide or optical fiberconfigured to direct EMR from an external source, an EMR source such asone or more diode lasers, a fiber laser, or the like. If the emitterarrangement includes a source of EMR, it can optionally include acooling arrangement configured to cool the EMR source(s) and preventoverheating of the source(s). A control arrangement can be provided tocontrol the operation of the emitter arrangement including, e.g.,turning the EMR source on and off, controlling or varying the poweroutput of the EMR source, etc.

The EMR can have a wavelengths that is preferably greater than about 600nm, e.g., between about 625 nm and about 850 nm, or between about 650 nmand 750 nm. Smaller wavelengths (e.g., less than about 600 nm) can bescattered significantly within the skin tissue, thereby havinginsufficient penetration depth to reach portions of the dermal layerwith sufficient fluence and focus. Such smaller wavelengths can alsohave a very high melanin absorbance, which can generate increased EMRabsorption by melanin in the overlying epidermal region and unwantedthermal damage to the surface region. Such smaller wavelengths can alsohave a higher absorbance by hemoglobin, a competing chromophore, whichmay be present in blood vessels. Significant EMR absorption byhemoglobin can cause unwanted thermal damage to such vessels. Absorbanceof EMR by melanin generally decreases with increasing wavelength, sowavelengths longer than about 850 nm may not be sufficiently absorbed bythe dermal melanin to cause local heating and disruption of thepigmented structures.

The exemplary apparatus can include an optical arrangement configured tofocus the EMR in a highly convergent beam. For example, the opticalarrangement can include a focusing or converging lens arrangement havinga numerical aperture (NA) of about 0.5 or greater, e.g., between about0.5 and 0.9. The correspondingly large convergence angle of the EMR canprovide a high fluence and intensity in the focal region of the lens(which can be located within the dermis) with a lower fluence in theoverlying tissue above the focal region. Such focal geometry can helpreduce unwanted heating and thermal damage in the overlying tissue abovethe pigmented dermal regions. The exemplary optical arrangement canfurther include a collimating lens arrangement configured to direct EMRfrom the emitting arrangement onto the focusing lens arrangement.

The exemplary optical arrangement can be configured to focus the EMR toa focal region having a width or spot size that is less than about 200μm (microns), for example, less than 100 μm, or even less than about 50μm, e.g., as small as 10 μm. Such spot size can be selected as a balancebetween being small enough to provide a high fluence or intensity of EMRin the focal region (to effectively irradiate pigmented structures inthe dermis), and being large enough to facilitate irradiation of largeregions/volumes of the skin tissue in a reasonable treatment time.

The exemplary optical arrangement can also be configured to direct thefocal region of the EMR onto a location within the dermal tissue that isat a depth below the skin surface of between about 120 μm and 400 μm,e.g., between about 150 μm and 300 μm. Such exemplary depth range cancorrespond to typical observed depths of pigmented regions in skin thatexhibits dermal melasma. This focal depth can correspond to a distancefrom a lower surface of the apparatus configured to contact the skinsurface and the location of the focal region.

In further exemplary embodiments of the present disclosure, thepositions and/or orientations of the EMR emitter arrangement and/orcomponents of the optical arrangement can be controllable or adjustablerelative to one another, such that the path of the EMR can be varied.Such variation in the path of the EMR can provide correspondingvariations in the depth, width, and/or location of the focal regionwithin the dermis, and can facilitate treatment of larger volumes of theskin tissue when the apparatus is translated with respect to the skin.Such relative movement of these components can also facilitate movementof the focal region within the skin tissue when the apparatus is heldstationary relative to the skin, e.g., to treat larger regions of theskin without moving the overall apparatus.

In still further exemplary embodiments of the present disclosure, theexemplary focusing lens arrangement can include a plurality ofmicro-lenses, e.g., convex lenses, plano-convex lenses, or the like.Each of the micro-lenses can have a large NA (e.g., between about 0.5and 0.9). The micro-lenses can be provided in an array, e.g., a squareor hexagonal array, to produce a plurality of focal regions in thedermal tissue in a similar pattern. A width of the micro-lenses can besmall, e.g., between about 1 mm and 3 mm wide. Micro-lenses 300 that areslightly wider or narrower than this can also be provided in certainembodiments. In yet further exemplary embodiments of the presentdisclosure, the micro-lenses can include cylindrical lenses, forexample, convex cylindrical lenses or plano-convex cylindrical lenses. Awidth of such cylindrical micro-lenses can be small, e.g., between about1 mm and 3 mm wide. A length of the cylindrical micro-lenses can bebetween, e.g., about 5 mm and 5 cm.

The exemplary radiation emitter arrangement and/or the exemplary opticalarrangement can be configured to direct a single wide beam of EMR overthe entire array of such micro-lenses or a portion thereof tosimultaneously generate a plurality of focal regions in the dermis. Infurther exemplary embodiments, radiation emitter arrangement and/or theoptical arrangement can be configured to direct a plurality of smallerbeams of EMR onto individual ones of the micro-lenses. Such multiplebeams can be provided, e.g., by using a plurality of EMR sources (suchas laser diodes), a beam splitter, or a plurality of waveguides, or byscanning a single beam over the individual micro-lenses. If cylindricalmicro-lenses are provided, one or more beams of EMR can be scanned oversuch cylindrical lenses, e.g., in a direction parallel to thelongitudinal axis of such cylindrical lenses.

In yet another exemplary embodiment of the present disclosure, theexemplary cylindrical or spherical micro-lenses can different NA values,different sizes or radii, and/or different effective focal lengths thanone another. Such variations in the geometry and optical properties ofthe micro-lenses can facilitate irradiation of larger volumes of thedermis.

The plate configured to contact the skin surface can optionally beprovided as part of the focusing lens arrangement, e.g., it can beformed as the lower surface of a plano-convex lens or a plurality ofsuch micro-lenses. The plate can optionally be cooled, e.g., bypre-cooling it prior to use or with an active cooling arrangement (e.g.a Peltier device, a conductive cold conduit, or the like). Such coolingcan help protect the epidermis and upper portions of the dermis fromunwanted thermal damage. An optical gel or the like (e.g. glycerol or asimilar substance) can optionally be provided between the plate and theskin surface to reduce an optical index mismatch between the plate andthe skin, thereby improving transmission of the EMR into the skin.

In further exemplary embodiments of the present disclosure, theexemplary apparatus can include one or more sensors configured to detectcontact of the apparatus with the skin and/or speed of the apparatusover the skin surface during use. Such exemplary sensors can be coupledto a control arrangement of the EMR emitter or source, and adapted togenerate signals capable of varying properties of the EMR, e.g., byvarying the power emitted by the emitter arrangement based on thetranslational speed of the apparatus, by turning off the source(s) ofEMR when the apparatus is stationary relative to the skin surface ormoved away from the skin, etc. Such sensors and control arrangements canimprove safety of the apparatus by preventing excessive irradiation andunwanted thermal damage to the skin.

It can be preferable to limit irradiation time (dwell time) of aparticular location in the dermis to a short period of time, e.g., about1-2 milliseconds or less. Such short dwell times can be achieved, e.g.,by configuring the radiation emitter arrangement to provide discretepulses of EMR. The exemplary interval between such pulses of EMR can be,e.g., on the order of about 50 milliseconds or more to provide spatialseparation between regions of the dermis irradiated by successive pulseswhen the apparatus is translated over the skin. Short dwell times canalso be achieved by translating the apparatus over the skin during use,e.g., at speeds of about 1 cm/s or greater, such that the focal regiondoes not remain on a particular location in the dermis for longer than afew milliseconds. In further embodiments, optional sensors can also beused to control the EMR emitted by the apparatus to avoid longer localdwell times.

The power output of the exemplary emitter arrangement can be selected toprovide a local fluence within each focal region that is between about10-1000 J/cm² for EMR having a wavelength of about 650 nm, e.g., betweenabout 50-500 J/cm². The estimated fluence within the focal region can berelated to the spot size, local dwell time, and total beam power usingconventional equations. Larger or smaller local fluence values can alsobe used when using faster or slower scan speeds and/or with shorter orlonger dwell times, respectively. The fluence can be somewhat lower forshorter wavelengths (which is more readily absorbed by melanin) orlarger for longer wavelengths, for which EMR absorption by melanin isweaker.

In further embodiments of the disclosure, a method can be provided fortreating dermal melasma that includes focusing at least one beam of EMRonto at least one focal region within the dermis, to generate selectiveabsorption by pigmented cells or structures within the dermis whileavoiding unwanted heating and damage to unpigmented tissue and overlyingtissue. The EMR wavelength used, focal properties (e.g., NA value, focaldepth, spot size), scanning speeds and/or pulsed EMR properties, EMRbeam power, fluence within the focal region(s), etc., can be provided inaccordance with the various embodiments described herein.

These and other objects, features and advantages of the presentdisclosure will become apparent upon reading the following detaileddescription of exemplary embodiments of the present disclosure, whentaken in conjunction with the appended drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present disclosure willbecome apparent from the following detailed description taken inconjunction with the accompanying figures showing illustrativeembodiments, results and/or features of the exemplary embodiments of thepresent disclosure, in which:

FIG. 1A is a side view of an illustration of one or more radiationsbeing focused into pigmented dermal tissue;

FIG. 1B is an exemplary absorbance spectrum graph for melanin;

FIG. 1C is an exemplary absorbance spectrum graph for oxygenated anddeoxygenated hemoglobin;

FIG. 2 is a cross-sectional side view of a diagram of an exemplaryapparatus in accordance with exemplary embodiments of the presentdisclosure;

FIG. 2A is a cross-sectional side view of a diagram of another exemplaryapparatus in accordance with exemplary embodiments of the presentdisclosure;

FIG. 3A is a schematic side view of an arrangement of micro-lenses thatcan be used with certain exemplary embodiments of the presentdisclosure;

FIG. 3B is a schematic top view of a first exemplary arrangement of themicro-lenses shown in FIG. 3A;

FIG. 3C is a schematic top view of a second exemplary arrangement of themicro-lenses shown in FIG. 3A;

FIG. 3D is a schematic top view of an exemplary arrangement ofcylindrical micro-lenses that can be used with certain exemplaryembodiments of the present disclosure;

FIG. 3E is a schematic angled view of the exemplary arrangement ofcylindrical micro-lenses shown in FIG. 3D;

FIG. 3F is a schematic side view of a further exemplary arrangement ofthe micro-lenses that can be used with further exemplary embodiments ofthe present disclosure;

FIG. 4 is a schematic cross-sectional side view of a further exemplaryapparatus in accordance with still further exemplary embodiments of thepresent disclosure;

FIG. 5 is an exemplary biopsy image of pig skin tattooed with a melaninsolution to simulate the effects of dermal melasma;

FIG. 6A is an exemplary surface image of a region of pig skin tattooedwith a melanin solution to simulate the effects of dermal melasma; and

FIG. 6B is an exemplary surface image of the tattooed region of pig skinshown in FIG. 6A after it has been irradiated with focusedelectromagnetic radiation in accordance with exemplary embodiments ofthe present disclosure.

Throughout the drawings, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components, or portions of the illustrated embodiments. Similar featuresmay thus be described by the same reference numerals, which indicate tothe skilled reader that exchanges of features between differentembodiments can be done unless otherwise explicitly stated. Moreover,while the present disclosure will now be described in detail withreference to the figures, it is done so in connection with theillustrative embodiments and is not limited by the particularembodiments illustrated in the figures. It is intended that changes andmodifications can be made to the described embodiments without departingfrom the true scope and spirit of the present disclosure as defined bythe appended claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

According to certain exemplary embodiments of the present disclosure,devices and methods can be provided for treating dermal (or deep)melasma. For example, electromagnetic radiation (EMR) such as, e.g.,optical energy) at one or more particular wavelengths can be focusedinto the dermis, where the EMR can optionally be pulsed and/or scanned,such that the radiation is selectively absorbed by the pigmented cellsin the dermis. Such absorption of the energy, together with the focusinggeometry and scanning parameters, can selectively damage or destroy manyof the pigmented cells while reducing or avoiding damage to surroundingunpigmented cells and to the overlying epidermis.

An exemplary schematic side view of a section of skin tissue is shown inFIG. 1. The skin tissue includes a skin surface 100 and an upperepidermal layer 110, or epidermis, which can be, e.g., about 60-120 μmthick in the facial region. The dermis can be slightly thicker in otherparts of the body. The underlying dermal layer 120, or dermis, extendsfrom below the epidermis 110 to the deeper subcutaneous fat layer (notshown). Skin exhibiting deep or dermal melasma can include a populationof pigmented cells or regions 130 that contain excessive amounts ofmelanin.

In exemplary embodiments of the present disclosure, an electromagneticradiation (EMR) 150 (e.g., optical energy) can be focused into one ormore focal regions 160 that can be located within the dermis 120. TheEMR 150 can be provided at one or more appropriate wavelengths that canbe absorbed by melanin. The EMR wavelength(s) can be selected to enhanceselective absorption by the pigmented regions 130 in the dermis 120.

For example, a graph of an exemplary absorption spectrum for melanin isshown in the graph of FIG. 1B. The absorption of EMR by melanin isobserved to reach a peak value at a wavelength of about 350 nm, and thendecreases with increasing wavelength. Although absorption of the EMR bythe melanin facilitates heating and/or disruption of themelanin-containing regions 130, a very high melanin absorbance canresult in high absorption by pigment in the epidermis 110 and reducedpenetration of the EMR into the dermis 120. As illustrated in FIG. 1B,melanin absorption at EMR wavelengths that are less than about 500 nmare relatively high, such that wavelengths less than about 500 nm maynot be suitable for penetrating sufficiently into the dermis 120 to heatand damage or disrupt pigmented regions 130 therein. Such enhancedabsorption at smaller wavelengths can result in unwanted damage to theepidermis 110 and upper (superficial) portion of the dermis 120, withrelatively little unabsorbed EMR passing through the tissue into thedeeper portions of the dermis 120.

Another significant chromophore observed in skin tissue is hemoglobin,which is present in blood vessels. Hemoglobin can be oxygenated (HbO₂)or deoxygenated (Hb), where each form of Hemoglobin may exhibit slightlydifferent EMR absorption properties. For example, exemplary absorptionspectra for both Hb and HbO₂ are shown in the graph of FIG. 1C. Thesespectra indicate a high absorption coefficient for both Hb and HbO₂ atEMR wavelengths less than about 600 nm, with the absorbance decreasingsignificantly at higher wavelengths. Strong absorption of EMR directedinto skin tissue by hemoglobin (Hb and/or HbO₂) can result in heating ofthe hemoglobin-containing blood vessels, resulting in unwanted damage tothese vascular structures and less EMR available to be absorbed by themelanin.

Accordingly, it can be preferable to use EMR having wavelengths greaterthan 600 nm in certain exemplary embodiments of the present disclosure,e.g., about 625 nm or greater. Such wavelengths can increase selectivityof EMR absorption in the dermis, e.g., by reducing competing absorptionby hemoglobin, and by also avoiding excessive absorption of the EMR byepidermal melanin (as described above) such that the EMR can penetrateinto the dermis 120 and target pigmented regions 130 therein.

For example, longer wavelengths of EMR tend to be scattered more easilyby the non-homogeneous structure of skin tissue. Such scattering canreduce the effective penetration depth of EMR directed onto the tissue,and also inhibit focusing of the EMR beam 150 into a small focal region160 as described herein. Further, the absorbance of melanin continues todecrease with increasing wavelength, as indicated in the graph of FIG.1B. Thus, EMR having wavelengths less than about 750 nm or 850 nm bewell-focused in tissue to generate sufficient local intensity within thedermis 120, as well as sufficiently absorbed by dermal melanin todisrupt and/or damage pigmented regions 130.

Accordingly, exemplary embodiments of the present disclosure, it ispossible to provide or use EMR having one or more wavelengths betweenabout 600 nm and about 850 nm, e.g., between about 625 nm and about 800nm, which is mostly in the visible range of light. In certainembodiments, the wavelength can be between about 650 nm and 750 nm. Infurther exemplary embodiments of the present disclosure, wavelengthsless than about 600 nm or greater than about 850 nm may be used,although EMR having such wavelengths may be provided with sufficientfocusing and/or appropriate power and fluence, as described herein, toachieve sufficient quantity and selectivity of absorption by melanin inthe dermis.

In further exemplary embodiments of the present disclosure, an apparatus200, schematically illustrated in a diagram of FIG. 2, can be providedto treat dermal melasma in skin using EMR 150, e.g., optical energy. Forexample, the apparatus 200 can include a radiation emitter arrangement210, and an optical arrangement that can be provided between theradiation emitter arrangement 210 and the target tissue to be treated.For example, the optical arrangement can include a first lensarrangement 220 and a second lens arrangement 230. These exemplarycomponents can optionally be provided in a handpiece 250 or otherhousing or enclosure. The apparatus 200 can further include a plate 240having a lower surface configured to contact the surface 100 of the skintissue being treated. An actuator arrangement 260 can be provided tocontrol the operation of the apparatus 200, e.g., to activate and/orturn off the emitter arrangement 210, control or adjust certainoperational parameters of the apparatus 200, etc. A power source (notshown) for the radiation emitter arrangement 210 can be provided. Forexample, the power source can include a battery provided within thehandpiece 250, an electrical cord or other conductive connectionprovided between the emitter arrangement 210 and an external powersource (e.g. an electrical outlet or the like), etc.

The radiation emitter arrangement 210 can include, e.g., one or morelaser diodes, optical fibers, waveguides, or other components configuredto generate and/or emit EMR 150 and direct it toward or onto the opticalarrangement 220, e.g., onto the first lens arrangement 220. In certainexemplary embodiments of the present disclosure, the radiation emitterarrangement 210 can include one or more laser diodes that emit opticalradiation 150 having one or more wavelengths between about 600 nm and850 nm, e.g., between about 650 nm and 750 nm.

In further exemplary embodiments of the present disclosure, theradiation emitter arrangement 210 can include distal ends of one or morewaveguides (e.g., optical fibers) (not shown), where the waveguides canbe configured or adapted to direct EMR 150 from an external source (notshown) toward or onto the first lens arrangement 220. Such exemplaryexternal EMR source can be configured to provide or direct EMR 150 tothe radiation emitter arrangement 210 having one or more wavelengthsbetween about 600 nm and 850 nm, e.g., between about 650 nm and 750 nm.

In further exemplary embodiments of the present disclosure, theelectromagnetic radiation (EMR) 150 (e.g., optical energy) can befocused into one or more focal regions 160 that can be located withinthe dermis 120, as shown schematically in FIGS. 1A and 2. The exemplaryoptical arrangement can be configured to provide one or morehighly-convergent beams of EMR 150, where each such beam can be emittedfrom a lower portion of the apparatus 200 and converge to a narrowerfocal region 160 located at a particular distance below the lowersurface of the apparatus 200, e.g., below the lower surface of the plate240. Such convergence of the EMR 150 can produce a high local fluenceand intensity within the focal region 160, while irradiating theoverlying tissue (e.g. epidermis 110 and upper portion of the dermis120) at a lower fluence.

In one additional exemplary embodiment of the present disclosure, thefirst lens arrangement 220 can be adapted and/or configured to directEMR 150 from the emitter arrangement 210 towards or onto the second lensarrangement 230. The first lens arrangement 220 can include, e.g., oneor more lenses, reflectors, partially- or fully-silvered mirrors,prisms, and/or beam splitters. For example, the first lens arrangement220 can be configured to collimate or align the EMR 150 emitted from theemitter arrangement 210 onto the second lens arrangement 230, as shownin FIG. 2. The first lens arrangement 220 can include, e.g., anobjective lens or the like.

The second lens arrangement 230 can be configured and/or adapted toreceive EMR 150 from the first lens arrangement 220, and direct it intoone or more focal zones 160 within the dermis 120, as shown in FIG. 1.For example, the first lens arrangement 220 can be a collimating lens,and the second lens arrangement 230 can serve as a focusing lens thatincludes, e.g., a single objective lens as shown in FIG. 2, one or moreplano-convex lenses or cylindrical lenses, or the like. Variousexemplary embodiments of the optical arrangement that can be configuredto produce one or more focal regions 160 are described in more detailherein below.

For example, as shown in the exemplary illustration in FIG. 2, thehighly-convergent beam of EMR 150 is relatively “spread out” as it ispasses through the plate 240 (e.g., as it enters the surface 100 of theskin tissue when the apparatus 200 is placed on the skin to irradiateit). Geometrical, temporal, and power characteristics of the EMR 150 canbe selected as described herein, such that the fluence and intensity ofthe EMR 150 at and near the skin surface 100 are sufficiently low toavoid unwanted heating and damage to the surface tissue. The EMR 150 canthen be focused to a sufficient intensity and fluence within the focalzone 160 to facilitate significant absorption of the EMR 150 bypigmented regions 130 within or proximal to the focal region 160. Inthis manner, exemplary embodiments of the present invention can targetpigmented regions 130 within the dermis 120 to selectively heat anddisrupt or damage them, without generating unwanted damage in theoverlying tissue and surrounding unpigmented tissue.

Exemplary beam convergent angles of about 70-80 degrees are illustratedin FIGS. 1A and 2, although this approximate value is merely anexemplary one. In general, the convergent angle can be about 40 degreesor greater, e.g., even about 90 degrees or larger. Such non-narrowconvergence angles can generate a large local intensity and fluence ofEMR 150 at the focal region 160 while the corresponding fluence in theoverlying (and underlying) tissue may be lower due to the beamconvergence/divergence. It should be understood that other convergenceangles are possible, and are within the scope of the present disclosure.

Accordingly, the effective numerical aperture (NA) of the second lensarrangement 230 is preferably large, e.g., greater than about 0.5, suchas between about 0.5 and 0.9. The numerical aperture NA is generallydefined in optics as NA=n sin θ, where n is the refractive index of themedium in which the lens is working, and θ is one-half of theconvergence or divergence angle of the beam. The EMR 150 enters the lensthrough surrounding air, which has an index of refraction of about 1.Thus, an exemplary convergent half-angle θ of the beam of EMR towardsthe focal region 160, corresponding to a NA value between about 0.5 and0.9, can be between about 30 and 65 degrees. Thus, the exemplary rangeof the total convergence angle can be between about 60 and 130 degrees.

Larger values of the effective NA can provide a larger convergenceangle, and a corresponding greater difference in the local beamintensity and fluence between the tissue surface 100 and the focalregion 160. Accordingly, a larger NA value can provide a greater “safetymargin” by providing less intense irradiation levels to the overlyingtissue than to the pigmented regions 130, thereby reducing thelikelihood of generating thermal damage in the overlying tissue.However, a larger NA value can decrease the size of the focal region 160relative to the area of the incoming EMR beam, which can therebyirradiate a relatively smaller treatment volume of pigmented tissuewithin the dermis 120. Such smaller treatment volumes can reduce theefficiency of treating large areas of skin in a reasonable time.Exemplary NA values between about 0.5 and 0.9 can thus provide areasonable compromise between safety factor and treatment efficiency,although slightly larger or smaller values of the NA may be used incertain embodiments (e.g., by adjusting other system parametersappropriately, such as beam power, scanning speed, etc.).

A width of the focal region 160 (e.g., a “spot size”) can be small,e.g., less than about 200 μm, for example, less than 100 μm. In general,the focal region can be defined as the volumetric region in which theEMR 150 is present at a highest intensity. For example, the focal region160 may not be present as an idealized spot because of such factors asscattering of the EMR 150 within the tissue, aberrations ornonidealities in the optical components (e.g. lenses and/or reflectors),variations in the path of the incident rays of EMR 150, etc. Further,the focal region 160 can be spread over a small range of depths withinthe tissue, as shown schematically in FIGS. 1A and 2. In general, thesize and location of the focal region relative to the apparatus 200 canbe determined or selected based on properties and configuration of theoptical arrangement (e.g., the first and second lens arrangements 220,230), the characteristics of the EMR 150 provided by the emittingarrangement 210, and optical properties of the skin tissue beingtreated.

In certain exemplary embodiments, the width of the focal region 160 canbe less than 50 μm, e.g., as small as 10 μm. For example, a theoreticallower for the spot size can be approximated as 1.22λ/NA, where λ is thewavelength of the electromagnetic radiation and NA is the numericalaperture of a lens. For a wavelength of about 650 nm and a NA of 0.5,the theoretical minimum spot size is about 1.6 microns. The actual spotsize (or width of the focal region 160) can be selected as a balancebetween being small enough to provide a high fluence or intensity of EMR150 in the focal zone 160 (to damage pigmented cells 130), and beinglarge enough to irradiate a sufficiently large volume of the skin tissuein a short time. Also, a larger focal spot size can reduce thedifference in fluence between the focal region and the overlying tissuefor a given NA value, thereby increasing the possibility of unwantedheating and/or damage to overlying tissue.

For a particular exemplary NA value of the focusing lens arrangement230, the beam radius at the surface can be estimated as the focal depthmultiplied by the tangent of the half-angle of convergence provided bythe focusing lens. As an example, an NA value of 0.5 corresponds to aconvergence half-angle of about 30 degrees, for which the tangent is0.577. For an exemplary focal depth of 200 microns, the radius of theconverging EMR beam at the skin surface 100 is about 115 microns(0.577×200), such that the total beam width at the surface is about 230microns. The local fluence is inversely proportional to the localcross-sectional area of the beam for a particular beam energy.Accordingly, for a spot size (focal region width) of 20 microns, theratio of fluence at the focal region to that at the skin surface isabout (230/20), or about 130:1. The actual fluence ratio may be somewhatless due to absorption of some of the EMR energy between the skinsurface and the focal region. Nevertheless, this exemplary calculationindicates the relatively low fluence in the surface regions of the skin(as compared to the fluence in the focal region) that can be generatedwhen using a focusing lens having a high NA.

In further exemplary embodiments of the present disclosure, a pluralityof such focal regions 160 can be generated simultaneously by theexemplary apparatus and/or the focal region(s) 160 may be scanned ortraversed through the portions of dermis 120 containing pigmented cells130 to irradiate larger volumes of the dermis 120 in a reasonable time,as described in more detail herein.

In certain exemplary embodiments, the depth of the focal region 160below the skin surface 100 can be between about 120 μm and 400 μm, e.g.,between about 150 μm and 300 μm. This exemplary depth range cangenerally correspond to the observed depths of pigmented regions 130 inskin that exhibits dermal melasma. The focal depth can correspond to adistance from a lower contact surface of the apparatus 200 (e.g., thelower surface of the plate 240) and the focal region 160 of the EMR 150,because the plate 240 may flatten out the underlying tissue when placedon the skin surface 100. Accordingly, the depth of the focal region 160within the skin may be selected or controlled based on a configurationof the optical arrangement within the housing 250.

In various exemplary embodiments of the present disclosure, the EMR 150can be collimated (e.g., rays within the EMR beam are substantiallyparallel to one another), convergent, or divergent between the firstlens arrangement 220 and second lens arrangement 230. In still furtherexemplary embodiments, the radiation emitter arrangement 210 and/orcomponents of the optical arrangement (e.g., the first lens arrangement220 and/or the second lens arrangement 230) can be controllable oradjustable such that the path of the EMR 150 can be varied. Suchexemplary variation in the path of the EMR 150 can provide correspondingvariations in the depth, width, and/or location of the focal region 160within the dermis 120 when the apparatus is held stationary with respectto the skin.

For example, the position and/or angle of the EMR 150 can be shiftedrelative to the optical axis of a lens in the second lens arrangement230. Alternatively or additionally, the convergence or divergence of theEMR 150 entering or within the optical arrangement can be varied. Suchvariations in the EMR geometry and/or path can provide variations in thedepth and/or lateral position of the focal region(s) 160. In thismanner, larger volumes of the dermis 120 can be irradiated while theapparatus 200 is held stationary over the area of skin being treated.Such exemplary variation of the focus region characteristics canfacilitate treatment of a plurality of depth ranges and/or locationswithin the dermis 120 containing pigmented cells or defects 130.

Exemplary adjustment and/or alteration of the geometry and/or path ofthe EMR 150 can be achieved, e.g., using one or more translators,movable mirrors, beam splitters and/or prisms, or the like, which may becoupled to the radiation emitter arrangement 210, the first lensarrangement 220, and/or the second lens arrangement 230. Further, theseexemplary variations in locations of the focal region 160 can also becombined with a translation of the apparatus 200 over the area of skinbeing treated to irradiate larger volumes of the dermis 120, therebytargeting a greater number of pigmented cells 130 that can be present.

In further exemplary embodiments of the present disclosure, the secondlens arrangement 230 can include a plurality of micro-lenses 300, e.g.,as provided in a schematic side view of the exemplary configurationillustrated in FIG. 3A. For example, the micro-lenses 300 can includeany conventional type of convergent lenses, e.g., convex lenses, orplano-convex lenses such as those shown in FIG. 3A. The micro-lenses 300can be configured to focus EMR 150 into a plurality of focal regions 160within the underlying dermis 120, as illustrated in FIG. 3A.

Each of the micro-lenses can have a large NA (e.g., between about 0.5and 0.9), such that the EMR 150 converges from a relatively wide area ator near the skin surface 100 (with a relatively low intensity or localfluence) to a small width (with higher intensity or local fluence) inthe focal region 160 within the dermis 120. Such optical properties canprovide a sufficient intensity of EMR 150 within the focal region 160 todamage pigmented cells that absorb the radiation 150, while avoidingareas or volumes of high fluence or intensity away from the volume ofdermis 120 containing pigmented cells 130, thereby reducing likelihoodof damaging overlying, underlying, and/or adjacent volumes ofunpigmented skin tissue.

The micro-lenses 300 can be provided in a substantially square orrectangular array, such as that shown in the top view of such exemplaryconfiguration in FIG. 3B. According to further exemplary embodiments ofthe present disclosure, the micro-lenses 300 can be provided in ahexagonal array, as shown in FIG. 3C. Other exemplary patterns and/orshapes of the micro-lenses 300 can be provided in still furtherexemplary embodiments. A width of the micro-lenses 300 can be small,e.g., between about 1 mm and 3 mm wide. The exemplary micro-lenses 300that are slightly wider or narrower than this can also be provided incertain exemplary embodiments.

In additional exemplary embodiments of the present disclosure, theradiation emitter arrangement 210 and/or the first lens arrangement 220can be configured to direct a single wide beam of EMR 150 (such as,e.g., that shown in FIG. 2) over the entire array of micro-lenses 300 ora substantial portion thereof. Such exemplary configuration can generatea plurality of focal regions 160 in the dermis 120 simultaneously. Infurther exemplary embodiments, the radiation emitter arrangement 210and/or the first lens arrangement 220 can be configured to direct aplurality of smaller beams of EMR 150 onto individual ones of themicro-lenses 300. According to still further exemplary embodiments, theradiation emitter arrangement 210 and/or the first lens arrangement 220can be configured to direct one or more smaller beams of EMR 150 onto aportion of the array of micro-lenses 300, e.g. onto a single micro-lensor a plurality of the micro-lenses 300, and the smaller beam(s) can bescanned over the array of the micro-lenses 300, such that a plurality ofthe focal regions 160 can be generated sequentially ornon-simultaneously in the dermis 120.

In yet further exemplary embodiments of the present disclosure, themicro-lenses 300 can include cylindrical lenses, for example, convexcylindrical lenses or plano-convex cylindrical lenses, e.g., as shown inan exemplary top view in FIG. 3D and exemplary angled view in FIG. 3E.In the context used herein, ‘cylindrical’ does not necessarily requirethe rounded surface of the lens to be circular; it may have anelliptical or other smooth but non-circular profile in certainembodiments. Such cylindrical lenses can have a uniform profile in anycross-section that is perpendicular to the longitudinal axis of thelens.

A width of the cylindrical micro-lenses 300 can be small, e.g., betweenabout 1 mm and 3 mm wide. The length of the cylindrical micro-lenses 300can be between about 5 mm and 5 cm, e.g., between about 5 mm and about 2cm. This width and length can be selected based on such factors as thetotal power emitted by the radiation emitter arrangement 210, theoverall size of the array of micro-lenses 300, etc. In certain exemplaryembodiments, cylindrical micro-lenses 300 that are slightly shorter orlonger and/or slightly narrower or wider can be provided.

In certain exemplary embodiments of the present disclosure, any of theexemplary arrays of the micro-lenses 300 can be provided on (or formedas part of) the plate 240, as illustrated in FIG. 3E. Such configurationcan facilitate placement of the micro-lenses 300 close to the skinsurface 100, and also facilitate a more precise depth of the focalregions 160 within the dermis 120, e.g., when the plate 240 contacts theskin surface 100 during use.

In further exemplary embodiments of the present disclosure, theradiation emitter arrangement 210 and/or the first lens arrangement 220can be configured to direct a single wide beam of EMR 150 (such as thatshown in FIG. 2) over the entire array of cylindrical micro-lenses 300or a substantial portion thereof. Such exemplary configuration cangenerate and/or produce a plurality of the focal regions 160 in thedermis 120 simultaneously that are elongated in one direction (e.g.along the longitudinal axis of the cylindrical micro-lenses 300) andnarrow (e.g., less than about 200 μm wide, less than about 100 μm wide,less than about 50 μm wide, or as small as about 10 μm wide) in adirection orthogonal to the longitudinal axis of the cylindricalmicro-lenses 300. Such “line-focused” EMR 150 can be used to moreefficiently irradiate larger volumes of the dermis 120, e.g., when theexemplary apparatus 200 is scanned over the area of skin being treated,for example, in a direction substantially orthogonal to (or optionallyat some other angle to) the longitudinal axis of the cylindricalmicro-lenses 300.

According to yet additional exemplary embodiments of the presentdisclosure, the radiation emitter arrangement 210 and/or the first lensarrangement 220 can be configured to direct one or more smaller beams ofEMR 150 onto one or more of the cylindrical micro-lenses 300. Forexample, the EMR 150 can be directed onto one or more cylindricalmicro-lenses 300, e.g., over an elongated area 320 such as that shown inFIG. 3D. The radiation emitter arrangement 210 and/or the first lensarrangement 220 can be further configured to scan or traverse theirradiated area 320 over the cylindrical micro-lenses 300 (for example,using one or more movable mirrors, prisms, waveguides, or the like inthe optical arrangement), e.g., along the longitudinal directionsindicated by the arrows shown in FIGS. 3D and 3E (or back and forthalong such direction), such that a plurality of the elongated focalregions 160 are progressively generated in the dermis 120 during thescan. Such scanning of the EMR 150 can produce an irradiated focalregion 160 having a shape of an extended line within the dermis 120. Theapparatus 200 can also be traversed laterally over the region of skinbeing treated, e.g., in a direction not parallel to the longitudinalaxes of the cylindrical micro-lenses 300, during the irradiation suchthat the elongated focal regions 160 can travel through the dermis 120and irradiate a larger volume of tissue. For example, as describedherein such lateral traversal can be between about 5 mm/sec and 5cm/sec. The scanning speed of the EMR beam along the axes of thecylindrical can be larger, e.g., greater than about 10 cm/sec, toprovide a more uniform irradiation of such larger volumes of tissue. Thescan rate of the EMR 150 along the cylindrical lens axes, traversalspeed of the apparatus 200 over the skin, power of the EMR emitterarrangement 210, and width of the focal region 160 can be selected toprovide a local fluence generated within portions of the the dermis 120by the elongated focal region 160 that is within the exemplary fluenceranges described herein.

In yet further exemplary embodiment of the present disclosure, some ofthe cylindrical or spherical micro-lenses 300 can have different NAvalues, different sizes or radii, and/or different effective focallengths, e.g., as shown in the exemplary schematic diagram in FIG. 3F.The different focal depths of the micro-lenses 300 below the skinsurface 100 can be, e.g., between about 120 μm and 400 μm, for example,between about 150 μm and 300 μm. Such exemplary variations in the focallengths can produce focal regions 160 at different depths, which canresult in irradiation of larger volumes of the dermis 120 when theexemplary apparatus 200 is translated over the area of skin beingtreated, thereby targeting a greater number of pigmented cells 130 thatmay be present (e.g., irradiating both shallower and deeper pigmentedcells 130 in the dermis 120).

The window or plate 240, if present, can be configured and/or structuredto contact the surface 100 of the area of skin being treated. The lowersurface of the window 240 can be substantially planar, or it may beconvex or concave in further embodiments. The window 240 can providecertain benefits during operation of the apparatus 200. For example, thewindow 240 can facilitate precise positioning of the first and secondoptical arrangements 220, 230 relative to the skin surface 100, whichcan facilitate accurate control, selection and/or variation of thedepth(s) of the focal region(s) 160 within the skin.

The window 240 can further stabilize the soft skin tissue while it isbeing irradiated by the apparatus 200, which can facilitate control anduniformity of the irradiation profile. Pressure provided by the window240 on the skin surface 100 can also blanche (or remove some blood from)the volume of skin tissue being irradiated, thereby reducing the amountof pigmented structures present locally (e.g. blood-filled vesselscontaining hemoglobin). Such blanching can facilitate increasedselectivity of absorption of the EMR 150 by pigmented cells 130 whilereducing a risk of unwanted damage to blood vessels.

In exemplary embodiments of the disclosure, the window 240 can becooled, e.g., by pre-cooling it prior to using the apparatus 200 or byactive cooling using a conventional cooling arrangement (e.g. a Peltierdevice, a conductive cold conduit, or the like). Such cooling canfacilitate protection of the epidermis 110 and/or upper portions of thedermis 120 from unwanted damage while the pigmented cells 130 are beingirradiated and/or damaged.

According to certain exemplary embodiments of the present disclosure,the window 240 can be provided as part of the second lens arrangement230. For example, the second lens arrangement 230 can include a singleplano-convex lens, as shown in FIG. 2A, or a plurality of plano-convexlenses, such as those shown in FIGS. 3A and 3D. Such lenses can beaffixed to or formed as part of the window 240. The lower (planar)surface of such lenses can provide the benefits of the window 240 asdescribed herein, e.g., precise positioning of the second lensarrangement 230 relative to the skin surface 100 to control depth of thefocal regions 160 arrangements can be used in embodiments of the presentdisclosure.

The actuator arrangement 260 can be configured to activate and/orcontrol the radiation emitter arrangement 210 and/or an external EMRsource that provides radiation to the radiation emitter arrangement 210,such that the irradiation of an area of skin by the EMR 150 can becontrolled. The radiation emitter arrangement 210 and/or the exemplaryapparatus 200 can further include a conventional control arrangement(not shown) that can be configured to control and/or adjust theproperties of the EMR 150 directed onto the skin being treated.

For example, the apparatus 200 can include one or more sensors Sconfigured to detect contact of the apparatus 200 with the skin surface100 and/or speed or displacement of the apparatus 200 over the skinsurface 100 during use. Such exemplary sensors S can generate signalscapable of varying properties of the EMR 150, e.g., by varying the poweremitted by the radiation emitter arrangement 210 based on thetranslational speed of the apparatus 200, by turning off the source(s)of EMR 150 when the apparatus 150 is stationary relative to the skinsurface 100, etc. Such sensors S and control arrangements can beprovided as a safety feature, e.g. to prevent excessive irradiation andunwanted damage to the skin being treated, and are generally known inthe art. Further variations of such conventional sensing and/or controlarrangements can be used in embodiments of the present disclosure.

In general, it can be preferable to expose a particular location in thedermis to the focal region 160 for only a short period of time, e.g., toprevent local build-up of heat through absorption of the optical energyby melanin or other pigment. Long local irradiation times (or “dwelltimes”) can generate heat faster and to a greater extent than it cansafely diffuse into the surrounding tissue, which may lead to unwanteddamage to unpigmented tissue. Thus, short-duration, intense irradiationof small areas of pigmented features 130 within the dermis 120 candisrupt the pigment and improve the appearance of melasma while avoidingexcessive heat generation and unwanted thermal damage to surroundingunpigmented tissue. For example, typical sizes of pigmented cells orstructures can be on the order of about 10 microns, and local thermalrelaxation times can be on the order of about 0.1 to about 1-2milliseconds. Longer local dwell times at irradiation intensitiessufficient to heat and damage the pigmented structures 130 can build upheat locally faster than it can safely dissipate away.

Limiting irradiation times (dwell times) at a particular focal regionlocation can be achieved in various ways. In one exemplary embodiment,the radiation emitter arrangement 210 can be configured to providediscrete pulses of EMR 150 into the focal regions 160. The intervalbetween such pulses of EMR can be, e.g., on the order of about 50milliseconds or more even if the location of the focal region is movingthrough the skin tissue at a relatively slow speed of a few mm/s. Theseexemplary parameters can result in a distance between focal regions 160irradiated by successive pulses of, e.g., about 50-100 microns, whichcan be greater than a width of the focal region 160 itself. Accordingly,such general parameters can facilitate spatial and temporal separationof the successive irradiated focal regions 160, such that local thermalrelaxation can occur and buildup of excess heat can be avoided. The spotsize, pulse duration, and/or total pulse energy can be selected based onthe principles and guidelines described herein, using simplecalculations, to provide a sufficient fluence within the focal region160 to affect the pigmented structures 130 while maintaining asufficiently small dwell time (e.g. less than about 1-2 ms).

In further exemplary embodiments of the present disclosure, the focusedradiation 150 can be scanned over a region of skin affected by dermalmelasma, such that the focal region(s) 160 may irradiate and damage alarge number of the pigmented cells 130. Such scanning can be performedwith any of the embodiments described herein. The scanning can be donemanually, e.g., using a conventional method of translating a handpieceover the area of skin to be treated. Alternatively, the apparatus 200can optionally be coupled to a translating arrangement that can beconfigured to automatically move the apparatus (or certain componentsthereof) over an area of skin to be treated. Such automatic translationcan be provided as a pre-set pattern or as a random or semi-random pathover the skin. In still further embodiments, one or more of the opticalcomponents (e.g. the first and/or second lens arrangement 220, 230)and/or the radiation emitter arrangement can be translated within thehousing 250, such that the focal region(s) 160 can translate within thetissue while the housing 250 is held in a single position relative tothe skin.

Average scan speeds (or ranges of such speeds) can be determined basedon the general exemplary guidelines described herein. For example, for aparticular spot size (which can be determined primarily by theproperties of the optical arrangement), the local dwell (irradiation)time can be estimated as the spot size/width divided by thetranslational speed. As noted herein, such dwell time is preferably lessthan about 1-2 milliseconds to avoid local heat buildup and unwantedthermal damage of unpigmented tissue. Accordingly, a minimum scan speedcan be estimated as the width of the focal region 160 divided by 1millisecond. For example, a spot size of 10 microns (0.01 mm) wouldcorrespond to a minimum scan speed of 0.01 mm/0.001 seconds, or about 10mm/sec (1 cm/sec). Scan rates for line-focused beams (e.g., produced bydirecting an EMR beam onto a cylindrical lens) can be estimated in asimilar manner, e.g., where the width of the focal line corresponds tothe width of the focal region and the scan speed is in a directionperpendicular to the focal line, or for other scanning configurations.

A power output of the radiation emitter arrangement 210 can be selectedbased on several factors including, e.g., the EMR wavelength, thenumber, size, and/or depth of the focal region(s) 160, opticalcharacteristics and geometry of the first and second lens arrangements220, 230, etc. The power output can be selected such that the fluence inthe focal region 160 is sufficiently high to damage pigmented cells 130that absorb the EMR 150 for short exposure times, while fluence at otherdepths (e.g., in the epidermis 110) is sufficiently low to minimize oravoid unwanted damage there.

Based on some experimental observations, a local fluence within thefocal region 160 that may be sufficient to affect melanin-containingstructures (e.g., pigmented cells) can be between about 10-1000 J/cm²,for example, between about 50-500 J/cm², for EMR 150 having a wavelengthof about 650 nm. This range of effective local fluences can increaseslightly with increasing wavelength of the EMR 150 (and decrease withdecreasing wavelength), based on the decreasing absorption factor formelanin at larger wavelengths. Larger or smaller local fluence valuesmay also be provided when using faster or slower scan speeds, in furtherexemplary embodiments. Larger or smaller local fluence values can alsobe provided when using shorter or longer dwell times, respectively. Thelocal dwell time can preferably remain less than about 1-2 millisecondsin such embodiments.

The exemplary fluence values and dwell times described herein can beunderstood to correspond to a single pulsed exposure onto, or a singletraversal of a scanned focal region through, a particular locationwithin the dermis. For example, a particular location within the dermis120 may be irradiated by scanning more than one focal region 160 throughit at different times, thereby providing a higher fluence at thatlocation. However, local heat build-up can be avoided by providing atime interval between successive irradiations of the same location thatis greater than a few milliseconds.

The total power output of the radiation emitter arrangement 210 directedonto a single focal spot 160 can thus be estimated and/or determinedbased on the focal spot size and scan speed. The fluence F (e.g., inJ/cm²) can be calculated as the EMR power output P multiplied by thedwell time z and divided by the focal spot area A (i.e., F=P τ/A), wherethe dwell time τ can be estimated as the focal spot width D divided bythe scan speed ν (i.e., τ=D/v). As an exemplary calculation, for EMR 150having a wavelength of about 650 nm, a focal spot width of about 20microns, and a scan speed of about 1 cm/s, the power output P of asingle EMR source (e.g., a laser diode) to achieve a level of localfluence in the focal region between about 10-1000 J/cm² is between about15 mW and 1500 mW.

Typical scan speeds for a handpiece that is manually translated over anarea of skin to be treated can be, e.g., on the order of about 5 mm/secto about 5 cm/sec. Such speeds correspond to traversing a distance of 5cm (about 2 inches) in about 1-10 seconds. Accordingly, for a handpiecethat is translated manually over the skin to irradiate portions of thedermis as described herein, the power output and focal geometry of theapparatus 200 can be selected to provide a fluence at the irradiatedlocations within the dermis that is within the general range describedherein.

Such exemplary power calculations can be based on the entire output ofthe laser diode being focused into one focal region. If the output froma single source of EMR is focused onto a plurality of focal regions(e.g., when using an optical splitter or a wide beam directed onto aplurality of micro-lenses), then the power output of the EMR source canbe multiplied by the number of focal spots 160 to achieve the same localfluence within each focal region 160. EMR 150 can be provided as acontinuous wave (CW) or optionally as a plurality of pulses.Alternatively, a plurality of EMR sources (e.g. laser diodes or thelike) can be provided to generate a plurality of irradiated focalregions 160 simultaneously, with the appropriate power level for eachEMR source being estimated as described above. In certain embodiments,if one or more EMR beams are scanned over the focusing lens arrangement230, the power of the EMR source can be selected based on the lensproperties, scan speed, etc. to provide fluences and dwell times atlocations of the dermis irradiated by the focal regions 160 that arewithin the general ranges described herein.

In certain exemplary embodiments of the present disclosure, theradiation emitter arrangement 210 can include a plurality of EMRemitters (e.g., laser diodes or waveguide ends). Such emitters can beprovided in a linear array, such that they lie substantially along oneor more straight lines. In further exemplary embodiments, the emitterscan be arranged in a two-dimensional pattern, which can provide furtherpatterns of EMR 150 directed onto the first lens arrangement 220. Asdescribed above, the power output of each emitter can be selected usinga routine calculation based on the focal spot size and scan speed togenerate a local fluence within each focal zone 160 that is within thepreferred range described herein.

A schematic diagram of a further exemplary apparatus 400 in accordancewith certain exemplary embodiments of the present disclosure is shown inFIG. 4. The exemplary apparatus 400 can be generally similar to theapparatus 200 shown in FIG. 2, and illustrates a few further featureswhich may also be provided in the apparatus 200 such as, e.g., a coolingarrangement for the EMR source or a lens cage. Exemplary features of theexemplary apparatus 200 can also be used with the exemplary apparatus400, including but not limited to an array of micro-lenses 300, ahousing 250, etc.

The apparatus 400 includes a lens cage 410 that can be provided as anenclosure or housing that encloses optical lenses 420, 430. A window 240can be provided at one end of the lens cage 410. An aspheric focusinglens 420 can be used in certain embodiments to provide a larger frontsurface working distance than, e.g., a microscope objective lens. Thedistance between the front of the focusing lens 420 and the targettissue may be less than about 1 cm for large NA values as describedherein, such that the window 240 can also protect the lens 4 fromcontacting the tissue directly. The NA of the aspheric focusing lens 420can optionally be selectable, e.g. to vary the focal depth beyond thewindow 240.

The exemplary apparatus 400 further includes a laser diode (LD) mountingarrangement 440 coupled to the lens cage 410, which can accept one ormore laser diodes 450 that can be selected to emit energy in the visibleand/or NIR ranges. A driver 460 for the laser diode(s) 450 can beprovided, and the laser diodes 450 can be held slightly above thresholdduring operation with an applied DC bias current, which can facilitate arapid rise-time in the pulse activation of the diode(s) 450. The pulseproperties can be controlled by a pulse generator arrangement 470, e.g.a programmable function generator that can be configured to control thelaser diode(s) 450 to produce single pulses or sequences of pulses, withselectable pulse widths (e.g. 30 ns and greater) and intervals betweenpulses.

The LD mounting arrangement 440 can also include a thermoelectric cooler(TEC) arrangement coupled or connected to the laser diode mountingarrangement 440, which can be controlled (e.g. with a TEC controller480) to prevent the laser diode(s) 450 from overheating during use. Theapparatus 400 (as well as the apparatus 200 shown in FIG. 2) can be usedin various orientations, e.g., vertically, horizontally, etc., with thewindow 240 pressed against a tissue provided at any angle to preciselyposition the optics relative to the tissue surface and therebyfacilitate control of the focal depth of the beam within the tissue.

The exemplary apparatus 200 shown in FIG. 2 and the exemplary apparatus400 shown in FIG. 4 are illustrations of exemplary configurations, andother embodiments using various combinations and/or configurations ofsimilar components can also be used. For example, different numbersand/or types of optical arrangements 220, 230 and/or emitterarrangements 210 can be used to provide irradiation characteristics andfocal regions 160 within the dermis 120 as described herein. Forexample, in certain embodiments, the apparatus 200 can be provided in ashape factor similar to that of a handheld razor, with the radiationemitter arrangement 210 provided as one or more laser diodes, opticalarrangements 220, 230 provided in the “head” of the razor, and a powersource (e.g. one or more conventional alkaline cells or the like)provided in the handle. Other form factors can also be used in furtherembodiments of the disclosure. Similar features, combinations and/orvariations can be provided for the apparatus 400.

Exemplary properties of the radiation emitter arrangement 210, such as,e.g., wavelength(s) of EMR 150, power or intensity of the EMR 150, sizeand numerical apertures of the optical arrangements 220, 230, scanningspeed or rate of the first optical arrangements 220 (if present), and/ortarget scan speed (or range thereof) of the apparatus 200 over the areaof skin being treated, can be selected to provide appropriate fluence,intensity and/or dwell time of the EMR 150 on the pigmented cells duringoperation of the apparatus 200. Exemplary values and/or ranges for suchparameters, as well as certain basic approaches that can be used toestimate their values as needed, are described in more detail herein.For example, such exemplary parameters can be selected to providesufficient local fluence at the pigmented cells 130 to damage them andreduce the pigmented appearance of the skin, while avoiding unwanteddamage to the epidermis 110 and unpigmented volumes of the dermis 120.

The exemplary effective dwell time can be estimated using conventionaltechniques based on an approximate width of pigmented cells 130 of about10 μm and the local width (e.g., focal diameter or width) and speed ofthe focal region 160. The speed of the focal region 160 can be estimatedbased on a scan speed of EMR 150 provided by the first lens arrangement220 and/or radiation emitter arrangement 210 (if present), opticalgeometry of the optical arrangements 220, 230, and scan speed of theapparatus 200 over the area of skin being treated.

One or more exemplary parameters of the apparatus 200, 400 can beselected and/or adjusted once the other ones are known to provide a safebut effective irradiation of the pigmented cells 130 as describedherein. For example, the exemplary apparatus 200, 400 having knowngeometry (e.g. spot size or focal line width, and NA) of the lensarrangements 220, 230 or lenses 420, 430 (and internal scanning speed ofEMR beams, if present), and a particular wavelength of EMR 150 can beprovided. The power of the EMR source(s) can then be selected based on atarget range of scanning speeds of the apparatus 200 over the area to betreated. For example, the exemplary apparatus 200, 400 can be traversedover an area of skin at a speed between about 1-5 cm/s, whichcorresponds approximately to the speed at which a conventional razor istraversed over skin during shaving. Using these exemplary parameters andthe number of passes to be made over the treatment area, the local speedand dwell time of the focal region(s) 160 can be estimated, and a poweroutput of the radiation emitter arrangement 210 can be selected oradjusted to provide an effective local fluence within the focal region160 as described herein. Such calculations are routine and can be doneby a person of ordinary skill in the art.

In further exemplary embodiments of the present disclosure, a method forreducing the pigmented appearance of dermal melasma can be provided. Theexemplary method can include directing and focusing electromagneticradiation 150 as described herein onto a plurality of focal regions 160within the dermis 120 using an optical arrangement, such that the EMR150 is selectively absorbed by pigmented regions 130 to thermally damageor disrupt them, while avoiding unwanted thermal damage to unpigmentedregions and overlying tissue (e.g., the epidermis 110).

The EMR 150 can have a wavelength greater than about 600 nm, e.g.,between about 600 and 850 nm, or between 625 and 800 nm, or betweenabout 650 and 750 nm. A width of the focal region within the dermis canbe less than about 200 microns, e.g., less than about 100 microns, orless than about 50 microns. The spot size can be greater than thetheoretical lower limit of a few microns.

The EMR 150 can be focused using the optical arrangement, which caninclude one or more lens arrangements 220, 230. The focusing lensarrangement 230 having a high NA, e.g., between about 0.5 and 0.9, canbe used to focus the EMR 150 onto a focal region 160. Such NA values canfacilitate generation of high fluence in the focal regions 160 withinthe dermis 120 while avoiding large fluences that may generate unwanteddamage in the overlying tissue. Such focusing can be achieved using,e.g., the single focusing lens 230 (such as a convex objective lens or aplano-convex lens), a plurality of such lenses provided as an array ofmicro-lenses 300, one or more convex or plano-convex cylindrical lenses,or the like. The EMR 150 can be directed onto the focusing lensarrangements 230, and optionally scanned or pulsed over the one or morefocusing lens arrangements 230, to irradiate a plurality of focalregions 160 in the dermis 120, either simultaneously or sequentially.

In further exemplary embodiments of the present disclosure, an opticalgel or the like (e.g. glycerol or a similar substance) can be providedbetween the window 240 and the skin surface 100 as a topical applicationto the skin surface 100. Such a gel can reduce an optical index mismatchbetween the window 240 and the skin, and it may improve transmission ofthe EMR 150 from the apparatus 200 into the dermis 120. The gel can alsoreduce friction between the exemplary apparatus 200 and skin surface100, thereby facilitating a smoother translation of the apparatus 200over the area of skin being treated.

A particular location within the dermis 120 can be irradiated by thefocal region with an irradiation (dwell) time that is less than about 2milliseconds, e.g., to facilitate local thermal relaxation of tissuethat absorbs the EMR 150 and avoid local buildup of excess heat. Suchshort dwell times can be provided, e.g., by scanning an apparatus thatprovides the focused EMR 150 over the area of skin being treated, bypulsing the EMR source, and/or by moving components of the EMR source oremitter 210 and/or optical arrangement, such that the location of thefocal region(s) 160 within the dermis 120 varies with time.

The local fluence within the focal region 160 can be, e.g., betweenabout 10-1000 J/cm², e.g., between about 50-500 J/cm², for EMR 150having a wavelength of about 650 nm. This range of effective localfluences can increase slightly with increasing wavelength of the EMR 150(and decrease with decreasing wavelength), based on the decreasingabsorption factor for melanin at larger wavelengths. Such fluence can berelated to the focal properties of the optical arrangement (e.g., thefocal spot size), the translational speed of the focal region 160 withinthe dermis 120, pulse duration of the applied EMR 150, etc. The surfaceof the skin 100 can optionally be cooled to further prevent unwantedthermal damage in the epidermis and/or upper dermis.

The exemplary method and apparatus and the associated parametersdescribed herein can be generally based on a single pass of a focalregion 160 over a pigmented cell 130. The fluence needed to achieve thesame thermal damage effect based on a plurality of passes variesapproximately as the fourth root of the number of passes n. For example,a single pass of a focal region 160 over a pigmented cell 130 at aparticular fluence would have a similar effect as 16 passes made with afocal region 160 having half the particular fluence. Although a singlepass may be more efficient than a plurality of passes, the exemplaryapparatus 200, 400 can be configured to provide an effective fluenceafter a particular number of passes have been made. A plurality ofpasses can provide a greater safety margin to avoid unwanted damage tothe epidermis while damaging the pigmented cells 130, e.g., it canaccommodate a greater range of effective translation speeds of theapparatus 200 over the treated area for multiple passes as compared toif just a single pass is made. The number of passes of the focalregion(s) 160 through a particular location in the dermis 120 candepend, e.g., on the internal scan rate of EMR 150 over the second lensarrangement 230, if present, the number of focal regions 160 that maypass through a given location during one pass of the entire apparatus200 (e.g., a function of the number, size, and arrangement ofmicro-lenses 300, if present), as well as the number of times theapparatus 200 is translated over the area to be treated.

Other exemplary features and/or functions of the exemplary apparatus200, 400 described herein can also be used in conjunction with theexemplary disclosed methods for treating dermal melasma.

Example

An animal study using an exemplary spot-focused laser device and modelsystem were used to test the efficacy of treating deep melasma usingoptical radiation. The study was performed on a female Yorkshire pig, asdescribed below.

First, a deep-melasma condition was simulated by tattooing the dermisusing a melanin-based ink. The ink was prepared by mixing syntheticmelanin at a concentration of 20 mg/mL in a 50:50 saline/glycerolsolution. The resulting suspension was then agitated prior to beinginjected into 1 cm by 1 cm test sites on the animal subject using astandard tattoo gun. The tattooed sites were then allowed to settle overa period of a week to allow melanophages to phagocytoze the melaningranules in the dermis. The melanin left in the epidermis wassubstantially eliminated over this time period through natural bodilyprocesses.

An exemplary biopsy image from a tattooed site that was allowed tosettle as described herein, is shown in FIG. 5. The tissue sample wasstained with Fontana-Masson stain to better image any melanin present.The dark spots evident in the dermal layer in FIG. 5 appear to begenerally similar to those observed in patients having deep/dermalmelasma. No such dark spots were seen in biopsy samples taken fromuntattooed sites that were similarly stained. Accordingly, the tattooprocess described herein appears to provide a useful in vivo model ofdermal melasma.

An exemplary melasma treatment system was constructed based on exemplaryembodiments of the present disclosure described herein, which includes a200 mW continuous wave (CW) diode laser configured to emit opticalenergy having a wavelength of about 658 nm, mounted on an x-y scanningplatform. The scanner was capable of scanning speeds up to 15 mm/s. Thelaser beam was collimated and focused using two lenses having anumerical aperture (NA) of 0.62 to a depth of about 200 μm.

Test sites that were tattooed with melanin ink as described above, andcontrol sites that have only tattooed borders to outline them, were bothtreated by scanning the focused laser beam across the sites in 10parallel lines at different speeds. The control sites were scanned toassess any potential damage that may occur in unpigmented skin under thedifferent scanning conditions performed.

An exemplary tattooed test site is shown in FIG. 6A. This image showsthe test site after the tattoo has been allowed to settle for a week,just prior to scanning with the laser apparatus. The test site wasscanned with the laser at a speed of 1-3 mm/sec, using a 200 mW CWoutput. The same test site is shown in FIG. 6B two weeks after it wasscanned with the laser. There is a noticeable lightening of theappearance with no scarring or scabbing evident, even though only aportion of the tattooed area was irradiated with focused optical energy.These results indicate the general efficacy of the exemplary methods anddevices described herein for reducing the hyperpigmented appearance ofdeep/dermal melasma.

The foregoing merely illustrates the principles of the presentdisclosure. Various modifications and alterations to the describedembodiments will be apparent to those skilled in the art in view of theteachings herein. It will thus be appreciated that those skilled in theart will be able to devise numerous techniques which, although notexplicitly described herein, embody the principles of the presentdisclosure and are thus within the spirit and scope of the presentdisclosure. All patents and publications cited herein are incorporatedherein by reference in their entireties.

1-32. (canceled)
 33. An apparatus for selectively affecting a pigmented region in a layer of a skin tissue, comprising: a radiation arrangement including at least one laser configured to emit at least one electromagnetic radiation (EMR) beam; an optical arrangement including at least one lens configured to direct and focus the at least one EMR beam as a convergent beam into at least one focal region having a width less than 100 μm within a dermis layer of the skin tissue containing pigmented and unpigmented regions; a sensor configured to detect a speed of a translation of the apparatus over the surface of the skin tissue, and provide signals which are based on the detected speed to affect at least one property of the at least one EMR beam; and a controller configured to receive the signals from the first sensor and to control: a power output of the radiation arrangement so as to provide a fluence of the at least one EMR beam between 10 and 1000 J/cm² in the at least one focal region when the signals indicate that the apparatus is in motion over the surface of the skin tissue, and at least one of the radiation arrangement or the optical arrangement so as to scan the at least one EMR beam over an entirety of a treatment area of the skin tissue within the dermis layer, wherein a dwell time of the at least one EMR beam at the at least one focal region is 2 ms or less, and wherein, in operation, the at least one EMR beam (i) provides selective energy absorption by the pigmented regions of the skin tissue within the treatment area, and (ii) damages the pigmented regions while preventing damage to the unpigmented regions of the skin tissue within the treatment area and within an epidermal layer of the skin tissue overlying the at least one focal region.
 34. The apparatus of claim 33, wherein a wavelength of the at least one EMR beam is between 500 and 850 nm.
 35. The apparatus of claim 33, wherein the controller is configured to turn off the radiation arrangement when the apparatus is stationary relative to the surface of the skin tissue.
 36. The apparatus of claim 33, wherein a scan speed of the at least one EMR beam is between 5 mm/s to 5 cm/s.
 37. The apparatus of claim 33, wherein the optical arrangement comprises a plurality of lenses.
 38. The apparatus of claim 37, wherein a width of each one of the plurality of lenses is between 1 mm and 3 mm.
 39. The apparatus of claim 38, wherein at least two of the plurality of lenses have different focal lengths.
 40. The apparatus of claim 33, wherein the optical arrangement comprises a plate having a lower surface configured contact the surface of the skin tissue.
 41. The apparatus of claim 33, further comprising an additional sensor configured to (i) detect contact of the apparatus with the skin surface, and (ii) provide additional signals to affect at least one property of the at least one EMR beam based on the detected contact.
 42. The apparatus of claim 41, wherein the controller is configured to(i) receive the additional signals, and (ii) turn on the radiation arrangement when the apparatus contacts the skin surface.
 43. The apparatus of claim 33, wherein the optical arrangement has a numerical aperture that is between 0.5 and 0.9. 